Cytogenetic, cell genetic and recombinant DNA techniques will be employed in obtaining an understanding of fundamental biological principles potentially relevant to mental retardation. Gene mapping, principally of mouse and man, will be carried out to determine general principles regarding gene organization as well as to elucidate in detail the map of specific regions (such as the human X chromosome), especially relevant to mental retardation syndromes. Somatic cell genetic studies will be conducted of selected problems, such as cell fusion and cellular uptake of exogenous DNA, of potential importance to the analysis and management of inherited disorders. DNA studies of the mouse and human X chromosomes will be made in order to study the comparative evolution of various sequences and in order to examine the chemical basis of X-inactivation.